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. 1968 Sep 1;128(3):399–414. doi: 10.1084/jem.128.3.399

CELL WALL COMPOSITION AND VIRULENCE IN ESCHERICHIA COLI

Donald N Medearis Jr 1, Bruce M Camitta 1, Edward C Heath 1
PMCID: PMC2138529  PMID: 4875325

Abstract

Uridine diphosphate galactose 4-epimerase and phosphomannose isomerase-deficient mutants of Escherichia coli O111:B4 were studied to test the hypothesis that in E. coli a specific relationship exists between O antigenicity, virulence, and capacity to resist phagocytosis. The first mutant, designated J-5, produces a cell wall lipopolysaccharide, the side chains of which do not contain galactose, glucose, N-acetylglucosamine, or colitose. The second mutant produces a cell wall lipopolysaccharide which lacks only colitose. The capacity of these various organisms to kill mice was strikingly different. E. coli O111 was 1000 times as virulent as J-5, and 100 times as virulent as L-2. The capacity of the organisms to kill mice was correlated with their ability to resist phagocytosis and to persist in the peritoneal cavity. The parent strain of O111 resisted phagocytosis by macrophages in vivo and polymorphonuclear leukocytes in vitro. The mutants did not, and the organism most deficient in the saccharide component of its LPS was most susceptible to phagocytosis and least virulent. These results were corroborated by growing the mutants in appropriately supplemented media which permitted the synthesis of complete LPS, reversed the susceptibility to phagocytosis, and restored virulence. Finally, serological reactivity was consistent with previous observations which had demonstrated that the O antigenicity of E. coli is determined by the saccharide composition of its cell wall lipopolysaccharide. Despite the difference in the capacity of the various log-phase organisms to kill mice when injected intraperitoneally, purified lipopolysaccharides extracted from them did not differ significantly in their capacity to kill or produce fever. Thus virulence was shown to be independent of endotoxin activity which in turn seemed to be unrelated to the saccharide composition of the cell wall LPS. Collectively, these data provide at least a partial molecular definition of virulence in E. coli by demonstrating that the presence or absence of specific sugars in its cell wall lipopolysaccharide is a determinant of its antiphagocytic capacity and its virulence.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. COHN Z. A. Determinants of infection in the peritoneal cavity. I. Response to and fate of Staphylococcus aureus and Staphylococcus albus in the mouse. Yale J Biol Med. 1962 Aug;35:12–28. [PMC free article] [PubMed] [Google Scholar]
  2. ELBEIN A. D., HEATH E. C. THE BIOSYNTHESIS OF CELL WALL LIPOPOLYSACCHARIDE IN ESCHERICHIA COLI. I. THE BIOCHEMICAL PROPERTIES OF A URIDINE DIPHOSPHATE GALACTOSE 4-EPIMERASELESS MUTANT. J Biol Chem. 1965 May;240:1919–1925. [PubMed] [Google Scholar]
  3. ERLANDSON A. L., Jr, NEMER M. A., PEARSON I. A. CHARACTERISTICS OF VARIOUS EXPERIMENTAL HUMAN ADULT VIRULENT ESCHERICHIA COLI INFECTIONS IN MICE. J Infect Dis. 1964 Apr;114:163–168. doi: 10.1093/infdis/114.2.163. [DOI] [PubMed] [Google Scholar]
  4. Edstrom R. D., Heath E. C. The biosynthesis of cell wall lipopolysaccharide in Escherichia coli. VII. Studies on the structure of the O-antigenic polysaccharide. J Biol Chem. 1967 Sep 25;242(18):4125–4133. [PubMed] [Google Scholar]
  5. FOLEY M. J., SMITH M. R., WOOD W. B., Jr Studies on the pathogenicity of group A Streptococci. I. Its relation to surface phagocytosis. J Exp Med. 1959 Oct 1;110:603–616. doi: 10.1084/jem.110.4.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. FUKASAWA T., NIKAIDO H. Formation of phage receptors induced by galactose in a galactose-sensitive mutant of Salmonella. Virology. 1960 Jun;11:508–510. doi: 10.1016/0042-6822(60)90093-3. [DOI] [PubMed] [Google Scholar]
  7. JENKIN C. R., ROWLEY D. Opsonins as determinants of survival in intraperitoneal infections of mice. Nature. 1959 Aug 8;184(Suppl 7):474–475. doi: 10.1038/184474a0. [DOI] [PubMed] [Google Scholar]
  8. KUNIN C. M., HALMAGYI N. E. Urinary-tract infections in schoolchildren. II. Characterization of invading organisms. N Engl J Med. 1962 Jun 21;266:1297–1301. doi: 10.1056/NEJM196206212662502. [DOI] [PubMed] [Google Scholar]
  9. Lüderitz O., Staub A. M., Westphal O. Immunochemistry of O and R antigens of Salmonella and related Enterobacteriaceae. Bacteriol Rev. 1966 Mar;30(1):192–255. doi: 10.1128/br.30.1.192-255.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. MARTIN S. P., GREEN R. Methods for the study of surviving leukocytes: A. Preparation of cell suspension. Methods Med Res. 1958;7:136–138. [PubMed] [Google Scholar]
  11. NAKANO M. Mutants of Salmonella with unusually low toxicity for mice. Nature. 1962 Dec 15;196:1118–1119. doi: 10.1038/1961118a0. [DOI] [PubMed] [Google Scholar]
  12. NETER E. BACTERIOLOGY AND IMMUNE RESPONSE IN URINARY TRACT INFECTIONS. Pediatr Clin North Am. 1964 Aug;11:517–531. doi: 10.1016/s0031-3955(16)31580-2. [DOI] [PubMed] [Google Scholar]
  13. RANTZ L. A. Serological grouping of Escherichia coli. Study in urinary tract infection. Arch Intern Med. 1962 Jan;109:37–42. doi: 10.1001/archinte.1962.03620130039006. [DOI] [PubMed] [Google Scholar]
  14. ROWLEY D. Bactericidal activity of macrophages in vitro against Escherichia coli. Nature. 1958 Jun 21;181(4625):1738–1739. doi: 10.1038/1811738b0. [DOI] [PubMed] [Google Scholar]
  15. ROWLEY D. The role of opsonins in non-specific immunity. J Exp Med. 1960 Jan 1;111:137–144. doi: 10.1084/jem.111.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. ROWLEY D. The virulence of strains of Bacterium coli for mice. Br J Exp Pathol. 1954 Dec;35(6):528–538. [PMC free article] [PubMed] [Google Scholar]
  17. Roantree R. J. Salmonella O antigens and virulence. Annu Rev Microbiol. 1967;21:443–466. doi: 10.1146/annurev.mi.21.100167.002303. [DOI] [PubMed] [Google Scholar]
  18. SKURSKI A., SLOPEK S., MICHALSKA E., OBST B. Studies on the mechanisms of the phagocytic reaction. II. Phagocytosis and S-R dissociation of gram-negative bacilli. J Hyg Epidemiol Microbiol Immunol. 1959;3:389–392. [PubMed] [Google Scholar]
  19. SLOPEK S., SKURSKI A., MICHALSKA E., DABROWSKI L. Studies on the mechanisms of the phagocytic reaction. I. Phagocytosis and the antigenic structure of gram-negative bacilli. J Hyg Epidemiol Microbiol Immunol. 1959;3:382–388. [PubMed] [Google Scholar]
  20. SWEET A. Y., WOLINSKY E. AN OUTBREAK OF URINARY TRACT AND OTHER INFECTIONS DUE TO E. COLI. Pediatrics. 1964 Jun;33:865–871. [PubMed] [Google Scholar]
  21. WHITBY J. L., ROWLEY D. The role of macrophages in the elimination of bacteria from the mouse peritoneum. Br J Exp Pathol. 1959 Aug;40:358–370. [PMC free article] [PubMed] [Google Scholar]

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